This proposal is to request support for a Keystone Symposia meeting entitled New Paradigms in Cancer Therapeutics, organized by Arul M. Chinnaiyan and William R. Sellers, which will be held in British Columbia, Canada from March 23 - 28, 2010. The advent of genome-scale profiling technologies has opened up the possibility of comprehensively monitoring multiple layers of molecular aberrations in cancer. Alterations in the epigenome, genome, transcriptome, proteome and metabolome have all been observed in tumor development. A number of key molecular pathways have been found to be altered during cancer progression. Pivotal questions in the field include: Can these novel pathways alone or in combination be effectively targeted in cancer? Can we identify molecular signatures that will facilitate personalized medicine? What are the innovative therapeutic modalities that can be employed to target these pathways? The goal of this meeting is to tackle promising new targets for cancer therapy. These include targets such as recurrent gene fusions, epigenetic pathways, and metabolic networks. We will also explore the use of molecular marker panels to select patients for treatment. A number of approaches to therapeutic targeting will be discussed including novel biologics and RNA interference. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Integration of Developmental Signaling Pathways which will share a keynote address and a plenary session with this meeting.